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The oceans cover more than two-thirds of Earth. As the adage goes, we know more about the surface of the moon than we do about the bottom of the ocean. The sea’s ability to transition from dark, explosive rage to serene, crystal-clear calm has terrified and beguiled humanity since we first visited the beach.
Given the vast, untapped nature of Earth’s oceans, it makes sense to plumb their depths in the hunt for new and innovative treatments. Marine animals, plants, and microbes have evolved a unique portfolio of chemicals to defend themselves and aid communication. Scientists are keen to know more about these novel compounds.
Why look to the sea?
There are a number of reasons why life in the sea has developed a distinct selection of molecules. For instance, animals that are anchored to the floor and do not have armor plating, such as sponges and corals, need to find other ways to defend themselves. In many cases, chemicals are their weapon of choice.
Although there appears to be a great deal of promise in the planet’s seas, many of the potential avenues are long and winding, and there will be no quick wins.
Additionally, marine creatures tend to have relatively primitive immune systems, and some live in overcrowded habitats, such as coral reefs, where defending themselves is a full-time job. At the same time, organisms in the ocean need to attract some organisms and repel others.
They also need to coordinate reproduction by synchronizing the release of eggs and sperm into the environment. All of these things require active biological molecules. Animals and plants that dwell in the ocean sit and swim in a bath of bacteria, fungi, and other organisms intend on turning them into a meal or a home.
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This diversity of threats has forced evolution to mount increasingly complex chemical battles. Some of the resulting compounds might be useful for our own war against disease. Medical researchers’ fascination with the sea is nothing new. The first evidence of humans using medicines from the ocean comes from China in 2953 B.C.E.
During the reign of the emperor Fu Hsi, there was a tax on the profits that came from fish-derived medicine. Jumping forward a few thousand years to the 1950s, an organic chemist called Werner Bergmann isolated a number of nucleosides from a Caribbean species of sponge called Cryptotethya crypta.
Given the vast, untapped nature of Earth’s oceans, it makes sense to plumb their depths in the hunt for new and innovative treatments.
These chemicals inspired the creation of a new generation of drugs, with scientists deriving two drugs called Ara-A and Ara-C from these nucleosides. Doctors use Ara-A to treat herpes infections and Ara-C to treat acute myeloid leukemia and non-Hodgkin lymphoma.
Cancer treatments from beneath the waves
Despite years of research, cancer is still proving a tough nut to crack. Although treatment has improved vastly, scientists are keen to get their hands on new bioactive chemicals that might help in the fight. Some cancer researchers are dipping their toes in the ocean. Most recently, a group of researchers investigated molecules that they had extracted from lampreys — a jawless, parasitic fish with an ancient pedigree.
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In particular, they were interested in so-called variable lymphocyte receptors (VLRs). VLRs target the extracellular matrix (ECM), which is a network of molecules that runs between cells. The ECM carries out varied roles in the body. For instance, it provides structural support for tissues, helps cells and tissues bond together, and assists with cell-to-cell communication.
As VLRs target the ECM, researchers believe that they could serve as drug mules that can transport chemicals through the normally impenetrable blood-brain barrier and straight to the brain.
They theorize that if VLRs can bypass the blood-brain barrier — a roadblock to most drugs — they may be able to treat certain conditions, including brain cancer and stroke, more effectively. Their preliminary work in a mouse model produced encouraging results.
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The gap between chemical and clinic
Firstly, as with any experimental drug, there is a great leap between a culture dish in a laboratory and a patient. In a living creature, drugs do not always respond in the way that scientists expect. Secondly, many drugs have toxic side effects that make them unusable.
Medical researchers’ fascination with the sea is nothing new. The first evidence of humans using medicines from the ocean comes from China in 2953 B.C.E.
Neither of these problems is a dead end as pharmacologists and chemists can tweak molecules or design similar chemicals, but this is all time-consuming. Another considerable issue is generating sufficient quantities of marine-derived chemicals. Many of the species either cannot survive captivity or require highly specific, difficult-to-maintain environments.
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Again, this means that scientists need to find ways to replicate the molecules of interest, which is a long and complicated path. Talking on these issues, the authors of a review write that “the power of organic synthesis and medicinal chemistry will have to come to bear.” These are technical, expensive hoops to jump through.
In conclusion, although there appears to be a great deal of promise in the planet’s seas, many of the potential avenues are long and winding, and there will be no quick wins.
As humans heap increasing pressure on marine ecosystems, concerns about the health of our oceans are reaching fever pitch. It may well be that potential drugs of the future are vanishing before scientists have the chance to harvest them.